Three Centers Pressing for Causes of Chronic Fatigue Syndrome

Researchers at three medical centers in New Jersey, Massachusetts and Colorado are conducting sophisticated tests on patients with chronic fatigue syndrome and comparing notes in the first consistent, multidisciplinary approach intended to get to the bottom of the disorder.

The syndrome, which begins with flu-like symptoms and can lead to exhaustion lasting for years, remains a profound mystery, said Dr. Stephen E. Straus, chief of the medical virology center at the National Institute of Allergy and Infectious Diseases in Bethesda, Md., the agency financing the three million dollar research program.

"Doctors do not know the molecular basis of fatigue in anyone, much less a person with chronic problems," Dr. Straus said. "When people say they feel tired all the time and their doctors can't find anything wrong with them, they're told the problem is in their heads."

Theory on Cause

But many leading researchers are now convinced that patients are telling the truth, Dr. Straus said. One compelling reason stems from the recent research on cytokines, cells of the human immune system that have been isolated and turned into drugs to fight cancer and other diseases. When healthy volunteers are injected with cytokines, Dr. Straus said, they feel awful and exhausted, exactly as chronic fatigue patients do.

A leading hypothesis among researchers is that chronic fatigue results from abnormally activated cytokines. "We can find plenty of things wrong with these patients," he said, including depressed numbers of natural killer cells, elevated antibodies to childhood viruses and signs of hormone complexes that depress the immune system. "But we don't know what to relate these changes to" or how they compare with healthy people and patients with other diseases that involve fatigue, he said.

At the Chronic Fatigue Center in the Veterans Affairs Hospital of East Orange, N.J, a team led by Dr. Benjamin Natelson is looking for ways to diagnose the disorder in patients. "If most doctors can't find an abnormality in a lab test, they think it's the patient's fault," Dr. Natelson said. "One of the biggest problems with chronic fatigue has been physician arrogance."

The New Jersey center has found a possible way to diagnose chronic fatigue patients.

Difference in Breathing Noticed

By paying careful attention to people, Sue Ann Sisto, a physical therapist at the center, noticed that patients breathe from the upper body, rather than from the belly and abdomen as most people do. Further testing showed that chronic fatigue patients have abnormal vagal tone, meaning the major nerve that syncopates their breathing and heart rate is out of sync. Their hearts are not speeding up and slowing down at a normal pace.

'"This is a solid piece of evidence that something going on with these patients," Dr. Natelson said. "Their bodies seem to be conserving energy in strange ways."

At the Chronic Fatigue Center of Brigham and Women's Hospital in Boston, Dr. Anthony Komaroff is focusing on the cytokine hypothesis. One idea is that the disease stems from the reactivation of childhood viruses.

When any virus proliferates, the body responds by releasing a torrent of cytokines, substances that amplify the immune system and wage war against he invading agent, Dr. Komaroff said. "We used to think you felt terrible because the virus was attacking your cells," he said. " But that's not true. You'II feel terrible because your body is responding and you are caught in the crossfire. As cytokines hit their target, they also hit you.

During the attack, people feel exhausted and conserve energy by crawling into bed, Dr. Komaroff said. Meanwhile, the cytokines alter liver metabolism and literally break down human muscles to maintain protein.

"Recycling your own body is more efficient than getting new food," he said. "You go to sleep. The battle rages. Finally the immune system clears the body of virus. The attack is shut off."

In chronic fatigue patients, this does not happen, Dr. Komaroff said. "You are in permanent crossfire," he said, "perhaps because the immune system cannot clear the virus. Maybe it is a latent virus that shows lust enough of itself to raise an attack but is hiding so well, the body can't kill it."

Cytokines are very difficult to measure, Dr. Komaroff said. They are short-lived, are made in many tissues and no one understands their natural balance.

In Denver, researchers at the Chronic Fatigue Center at the National Jewish Center for Immunology and Respiratory Medicine are looking for patterns of symptoms in patients compared with healthy volunteers.

One set of complaints is that people feel cold and cannot sleep, said Dr. James Jones, director of the fatigue center. Each symptom is being measured. For example, volunteers swallow pill-sized thermometers that constantly radio relay core body temperatures as the devices pass through their bodies over a two-week period. They also spend nights in a sleep laboratory for careful study.

Trouble Concentrating

Another complaint is inability to concentrate. Batteries of neuropsychological tests are being given to tease out differences in thinking processes.

Patients say their muscles tire easily, Dr. Jones said. So researchers have devised a way to measure fatigue in muscles, independent of strength and conditioning.

A fourth area involves allergies, Dr. Jones said. Seventy percent of chronic fatigue patients have them, compared with 25 percent of the general population. Perhaps they have an exaggerated immune system, he said. Tests are under way to look at how each person's immune cells respond to common allergens.